Oncogenicity of Epstein-Barr virus (EBV) will be studied by biochemical methods. C-RNA-DNA membrane hybridization and DNA-DNA reassociation kinetics will be used to detect viral genomes in tumor biopsies and cell cultures derived from these biopsies. The genetic relationships between EBV and other herpestype viruses will be studied. The state of EBV-DNA in permanent carrier lines will be examined and attempts will be made to eliminate the viral genome from such carrier lines (integration and curing). Transcriptional regulation of EBV will be studied in non-productively infected cells, virus producing cell lines and tumor biopsies. Cell transformation by EBV will be evaluated in EBV-genome free leukocytes, diploid epithelial cells with a limited growth potential derived from both man and marmosets. A more accurate method for quantitating transformation by EBV will be developed. Activation of C-type virus genomes by EBV infection will also be studied. The passenger virus hypothesis will be tested by cytohybridization of tumor biopsies and by cloning of leukocyte cells derived from Burkitt's lymphoma and determining the number of EBV genomes per cell in each clone. If EBV is a causative agent, the number of genomes per cell should be identical in each non-productive clone because BL is an uniclonal tumor. The site of EBV replication in vivo will also be studied.